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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
131

Tryptophan and the kynurenine pathway in chronic renal failure patients on dialysis

Bipath, Priyesh 21 October 2008 (has links)
Tryptophan is metabolised along the kynurenine pathway under the influence of tryptophan 2,3 dioxygenase and indoleamine 2,3 dioxygenase. Quinolinic acid and kynurenine, two neuroactive metabolites of the kynurenine pathway are, in chronic renal failure patients, considered as uraemic toxins. Related research is generally hampered by the non-availability of relevant analytical techniques. The primary aim of this study was, therefore, to develop and validate suitable methods for the determination of tryptophan, kynurenine and quinolinic acid. The second aim was to quantify the levels of these substances in the blood of chronic renal failure patients on renal replacement therapies and to compare the levels of haemodialysis patients to those on peritoneal dialysis. Patients’ quality of life was investigated relative to disturbances in tryptophan metabolism. Gas chromatography coupled to mass spectrometry (GC-MS) gave the best results for the analysis of tryptophan, kynurenine and quinolinic acid. A Hewlett Packard HP GC 6890 series gas chromatographer was coupled to a MS 5973 series mass spectrometer. Analytes were separated on a DB-5MS column with a nominal length of 30 metres, a diameter of 250.0 µm and film thickness of 0.10 µm. Helium was used as carrier gas, and the chromatographic analysis run time 12.5 minutes. The validation results were within the acceptance criteria for newly developed methods. The linear calibration curves constructed for all of the analytes gave r2 correlation coefficients >0.99. Other validation data such as precision, bias, accuracy and stability all fell within acceptable validation limits. In the study on chronic renal failure patients significant differences were seen between patients and controls. Tryptophan levels were 5.34 SD 5.04 µM for the haemodialysis group, 6.73 SD 3.18 µM for the peritoneal dialysis group and 28.4 SD 4.31 µM for the control group. Kynurenine levels were 4.7 SD 1.9 µM for the haemodialysis group, 2.9 SD 2.0 µM for the peritoneal dialysis group and 2.1 SD 0.6 µM for the control group. Quinolinic acid levels were 4.9 SD 2.0 µM for the haemodialysis group, 2.8 SD 2.0 µM for the peritoneal dialysis group and 0.3 SD 0.1 µM for the control group. Tryptophan was lower for the total patient group than for controls with significantly lower levels for haemodialysis versus control (p<0.05) and peritoneal dialysis versus control (p<0.05). Kynurenine levels were higher in the total patient group with significantly higher levels for the haemodialysis versus control group (p=0.0001). The patient groups had higher quinolinic acid levels with significantly higher levels for the haemodialysis versus control (p<0.05) and peritoneal dialysis versus control (p<0.05) groups. This study was the first to determine the three substances simultaneously in both haemodialysis and peritoneal dialysis patients. The study showed significant tryptophan depletion, as well as kynurenine and quinolinic acid accumulation for both groups. No significant differences were found between the patient groups other than higher kynurenine levels in the haemodialysis group. The quality of life (SF-36) was largely similar in the two patient groups. This decrease in the quality of life strongly correlated with the degree of tryptophan depletion. / Dissertation (MSc)--University of Pretoria, 2008. / Chemical Pathology / unrestricted
132

The self-esteem of chronically ill adolescents

Lees, Nancy Berman 01 January 1991 (has links)
No description available.
133

Medical compliance for Hispanic patients with end stage renal disease

Cruz, Leo Joe 01 January 1999 (has links)
The scope of this project is an examination of medical compliance for the Hispanic patient with End State Renal Disease.
134

Development of strategies to increase participation of pharmacists in the renal multidisciplinary health care team at Polokwane Hospital, Limpopo Province

Moloto, Brilliant Noko January 2019 (has links)
Thesis (M. A. (PHARM.) -- University of Limpopo, 2019 / Introduction Multidisciplinary team (MDT) approach has emerged as one solution to improving chronic kidney disease (CKD) care. The MDT may include a nephrologist, physicians, nurses, dietitians, pharmacists, and social workers, all working together to deliver effective care to patients with CKD. Participation of pharmacists within the renal MDT at Polokwane hospital seems to be limited. The perceived barriers to pharmacists providing renal care services to CKD patients at Polokwane hospital could inform future strategy development, to enhance their participation. The aim of this study was to explore the role of pharmacists in renal care and develop strategies to maximise their participation in the renal multidisciplinary health care team, based on their participation at Polokwane hospital, Limpopo province. Method A qualitative study using semi-structured interviews was conducted with a purposeful sample of 8 members of the renal MDT and 9 pharmacists. The audiotaped interviews were transcribed exactly as said and analysed using thematic content analysis. Results Four themes emerged from the analysis: ‘pharmacist’s current scope of practice within the renal MDT’, ‘potential future roles of pharmacists’, ‘perceived barriers to participation of pharmacists within the renal MDT’ and ‘recommendation/Strategies to incorporate pharmacists into the MDT’. Results have shown that pharmacists have an absent role within the renal MDT. Their role is limited to just dispensing and managing stock, with no role in direct patient care. Both pharmacists and MDT members showed preference to working together during renal care. Pharmacy services suggested include medication reviews, provision of patient education and counselling, patient adherence improvement, dosage workouts, patient monitoring and education on contraindicated drugs and drug interactions. Shortage of staff, pharmacists lack of clinical skills, lack of communication and attitude of pharmacists were perceived as the major barriers to participation of pharmacists within the renal xii MDT. To overcome these barriers, it was recommended that the department of health (DoH) provide more pharmacy staff and educational opportunities in the form of workshops, to equip pharmacists clinically and broaden competency and knowledge on effective communication and coordination. In addition, it was recommended that the clinical curriculum at Universities be revised, to build solid foundation on MDT care and pharmacology and that the MDT programme be standardized through standard treatment guidelines (SOP’s), policies and drawing of job descriptions. Conclusion The role of pharmacists at Polokwane hospital is confined to just stock management and dispensing. There are promising avenues for future development of their role during patient care, which can be achieved by addressing the barriers highlighted Recommendations The expansion of the role of pharmacists within the renal MDT will require improved partnership between health care professionals, resources, legislations and guidance from formal SOPs. Having a national framework for pharmacy practice from Ministry of Health, supported by educational opportunities and a pro-active professional association would be key to incorporating pharmacists within the renal MDT.
135

"Toxic thoughts"- impact of chronic kidney disease on cognitive functioning and pyschological well-being

Ansell, Glen January 2016 (has links)
A research project submitted in fulfilment of the requirements for the degree of Master of Arts in Psychology through the Faculty of Humanities, University of the Witwatersrand, Johannesburg, 2016 / Background Chronic Kidney Disease (CKD) is a reality faced by many around the world. There has been much physiological study around factors associated with CKD, as well as many studies surrounding the psychosocial impacts of the disease, with relatively less attention given to neuropsychological effects the disease can have on sufferers. This paper investigates the cognitive impacts as well as psychological impacts simultaneously, impacting on sufferers of End Stage Kidney Disease (ESKD). Methods Sixteen medically stable patients aged (M = 40.56, SD = 12.52) years with ESKD, were investigated. Eight of the patients were evaluated before and after six months of successful kidney transplant, using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), which assessed immediate memory, visuospatial / constructional, language, and attention. They were also tested on a brief symptom inventory (BSI 18) to assess depression and anxiety in these patients. A further eight who remained on dialysis, and had not undergone renal transplant were evaluated in the same manner for comparative purposes. Results Between-group comparisons showed a statistically significant improvement in overall cognitive functioning, as well as in the specific cognitive domains of visuospatial / constructional, language and attention for participants who had undergone renal transplant surgery compared to their counterparts who had not. Results also found that there were no statistically significant differences between the levels of anxiety experienced between patients in the two groups. When assessing the differences in cognitive improvement within the transplant patient group before and after transplant, improvement in the delayed memory function of renal transplant patients post-transplant was found. Conclusion These data show improvements in delayed memory function of patients having undergone renal transplant therapy, while also highlighting a continued decline of overall cognitive functioning in patients remaining on hemodialysis therapy. / GR2017
136

Survival analysis of time-to-first peritonitis among kidney patients who are on peritoneal analysis at Pietersburg Provincial Hospital, Limpopo Province, South Africa

Maja, Tshepo Frans January 2020 (has links)
Thesis (M.Sc. (Statistics)) -- University of Limpopo, 2020 / Peritoneal Dialysis (PD) is a process of replacing kidney function which cleans waste from the blood and remove extra fluid from the body. In most cases, the process of PD is slowed down by a peritoneal membrane infection called peritonitis. Despite recent advancements in treatments and prevention, peritonitis still remains the leading complication which results in high morbidity and technique failure among PD patients. Using a prospective peritonitis dataset of 159 kidney patients who were on PD from 2008 to 2015 in Pietersburg Provincial Hospital, the aim of this study was to identify potential social, demographic and biological risk factors that contribute to the first episode of peritonitis. Both semi-parametric (Cox PH) and parametric (Accelerated Failure Time: Weibull, exponential, loglogistic, and gamma) survival models were fitted to the peritonitis dataset. Akaike Information Criterion (AIC) was applied to select models which best fit to the peritonitis data. Accordingly, log-logistic Accelerated Failure Time (AFT) model was found to be a working model that best fit to the data. A total of 96 (60.38%) peritonitis cases were recorded over the follow-up period with majority of peritonitis infection coming from females (65.4%) and rural dwellers (65.7%) with (62.6%) of black Africans showing higher risk of developing peritonitis. The multivariate log-logistic AFT model revealed that availability of water (p-value=0.018), electricity (p-value=0.018), dwelling (p-value=0.008), haemoglobin status (p-value=0.002) and duration on PD (p-value=0.001) are significant risk factors for the development of peritonitis. Therefore, patients with no water and electricity, coming from rural background with low level of haemoglobin and shorter duration on PD are associii ated with high risk or hazard of developing peritonitis for the first time.
137

Improving health communication : an anthropological perspective of health literacy among chronic disease patients

van Bronkhorst, Kelly Marie 01 December 2011 (has links)
This research examines the relationship between health literacy among End Stage Renal Disease (ESRD) patients and its relevance for communication between patients and providers. The study was conducted among dialysis services providers at the Good Samaritan Dialysis Center and dialysis patients receiving care at the Center. Data collection techniques included individual interviews, surveys, and the Short Test of Functional Health Literacy in Adults (S-TOFHLA), which measured the health literacy level of the participants. The results of the study show that a large majority of the patients have "adequate" health literacy, which contradicts the provider's perceptions of the patient's ability to comprehend health information. Provider's perspectives are shaped by their training and work environment. The study suggests that structural barriers and communication issues impede effective patient-provider interactions. This issue is especially serious for those chronic disease patients who have limited self-management skills. / Graduation date: 2012
138

O impacto social da hemodiálise para classe trabalhadora /

Silva, Márcia Cristina Freitas. January 2010 (has links)
Orientador: Iris Fenner Bertani / Banca: Cléria Maria Lobo Bittar Pucci Bueno / Banca: Fernanda de Oliveira Sarreta / Resumo: As doenças crônicas têm recebido maior atenção dos profissionais nas últimas décadas. Isso se deve ao importante papel desempenhado na morbimortalidade da população mundial e no Brasil. Entre essas doenças, está a insuficiência renal crônica, que se traduz em uma série de mudanças na vida dos trabalhadores e está em evidência na atualidade. Os usuários em diálise encontram-se privados muitas situações e atividades que interferem em sua qualidade de vida, apesar dos avanços tecnológicos da hemodiálise. O presente trabalho tem como objetivo conhecer o impacto social decorrente do processo de hemodiálise na vida dos trabalhadores com insuficiência renal crônica. A metodologia utilizada é a pesquisa exploratória, por meio de entrevista semiestruturada com 6 (seis) sujeitos em programa de hemodiálise, de ambos os sexos, na faixa etária de 20 a 45 anos, em período inicial de tratamento. O estudo tem natureza quanti-qualitativa, com dados obtidos pela análise documental e utiliza como base a orientação teórica do materialismo histórico-dialético. Os resultados dão visibilidade às expressões da questão social implicadas no processo de saúde-doença do sujeito em hemodiálise, decifrando a realidade, ampliando o conhecimento no campo de trabalho e suas particularidades, onde o impacto constitui um paradoxo, pois de um lado estão presentes o alívio dos sintomas da doença e a sobrevida e, de outro, a dependência do tratamento, as restrições e os reflexos que afligem a vida do usuário e de sua família, gerados por um sistema econômico que viola os direitos de saúde da classe trabalhadora / Abstract: Chronic diseases have received increased attention of professionals in recent decades. This is due to the important role played in morbi-mortality of the world population and in Brazil. Among these diseases are chronic renal failure, which translates into a series of changes in workers' lives and is in evidence today. Users on dialysis are deprived in many situations and activities that interfere with their quality of life, despite the technological advances of hemodialysis. This study aims to evaluate the social impact of the process of hemodialysis on workers with chronic renal failure. The methodology employed is the exploratory research, using semistructured interviews with 6 (six) patients on hemodialysis, both sexes, aged from 20 to 45 years in the early period of treatment. The study has both quantitative and qualitative elements, with data obtained by the documental analysis and uses as a basis theoretical orientation of the historic- dialectical materialism. The expected results give visibility to expressions of social issues involved in the process of health and illness of the patient in hemodialysis, deciphering the reality, expanding knowledge in the field of work and its peculiarities, where the impact is a paradox, because on one side are presents the symptom relief of the disease and survival and, secondly, the dependence on treatment, restrictions and reflections that affect the user's life and his family, generated by an economic system that violates the rights of health of the working class / Mestre
139

Influência do Diabetes mellitus e da insuficiência renal crônica em tratamento dialítico na farmacocinética e farmacodinâmica do carvedilol em pacientes hipertensos / Influence of Diabetes mellitus and chronic renal failure on continuous ambulatory peritoneal dialysis on the pharmacokinetics and pharmacodynamics of carvedilol in hypertensive patients

Silva, Flávia Garcez da 29 August 2008 (has links)
O carvedilol é um fármaco utilizado na terapêutica da hipertensão e da insuficiência cardíaca congestiva. É disponível para uso clínico como racemato e seus enantiômeros apresentam atividade semelhante sobre os receptores 1-adrenérgicos, sendo que o enantiômero S-(-) é mais ativo como antagonista dos receptores adrenérgicos. O presente estudo visa investigar a influência do Diabetes mellitus (DM) tipo 2 e da insuficiência renal crônica (IRC) em pacientes em diálise peritoneal ambulatorial contínua (DPAC) na farmacocinética enantiosseletiva e na farmacodinâmica do carvedilol em pacientes hipertensos. Os pacientes hipertensos investigados divididos nos grupos controle (n=8), DM tipo 2 (n=8) e IRC em DPAC (n=6) receberam dose única p.o. de 25 mg de carvedilol racêmico. Os enantiômeros do carvedilol e metabólitos 4-hidroxifenil e O-desmetilcarvedilol foram analisados no sistema LC-MS/MS empregando coluna quiral e fase móvel constituída por mistura de metanol: ácido acético: dietilamina. O método foi linear no intervalo de concentrações de 0,1-100 ng de cada enantiômero do carvedilol/mL de líquido de diálise, 0,2-200 ng de cada enantiômero do carvedilol/mL de plasma, 2,5-2500 ng de cada enantiômero do carvedilol, 4-hidroxifenil e O-desmetilcarvedilol/mL de urina. Os parâmetros farmacocinéticos foram calculados empregando o programa WinNonlin. O teste de Wilcoxon foi usado para avaliar as razões enantioméricas dentro dos grupos e o teste de Mann-Whitney foi utilizado para avaliar as diferença dos parâmetros farmacocinéticos entre os grupos. Na investigação do fenótipo oxidativo tipo metoprolol todos os pacientes incluídos no estudo foram fenotipados como metabolizadores extensivos. Os pacientes investigados com DM tipo 2 comparados com o grupo controle não apresentaram alterações na farmacocinética e farmacodinâmica (PK-PD) do carvedilol. Os pacientes com IRC em DPAC apresentaram valores de clearance (CL/F) dos enantiômeros R-(+) - e S-(-)-carvedilol de 25,17 e 27,89 L/h, respectivamente, sendo significativamente inferiores aos obtidos para os pacientes do grupo controle (76,76 e 142,0 L/h). As razões de AUCR/S foram de 2,27 para os pacientes do grupo controle e de 0,97 para os pacientes com IRC em DPAC. Os pacientes com IRC em DPAC não mostraram enantiosseletividade na farmacocinética do carvedilol em razão do acúmulo plasmático preferencial do enantiômero com atividade -bloqueadora S-(-)-carvedilol. / Carvedilol is used for the treatment of hypertension and congestive heart failure. The drug is available for clinical use as the racemate and its enantiomers exert similar activity on 1-adrenergic receptors, whereas the S-(-) enantiomer is more active as a -adrenergic receptor antagonist. The aim of the present study was to investigate the influence of type 2 Diabetes mellitus (DM) and chronic renal failure (CRF) on patients receiving continuous ambulatory peritoneal dialysis (CAPD) on the enantioselective pharmacokinetics and pharmacodynamics of carvedilol in hypertensive patients. The hypertensive patients were divided into a control (n=8), type 2 DM (n=8) and CRF on CAPD (n=6) group and received a single oral dose of 25 mg racemic carvedilol. The enantiomers of carvedilol and of the metabolites 4-hydroxyphenyl and O-desmethylcarvedilol were analyzed by LC-MS/MS using a chiral column and a mobile phase consisting of a mixture of methanol:acetic acid-diethylamine. The method was linear within the following concentration ranges: 0.1-100 ng of each carvedilol enantiomer/mL dialysis fluid, 0.2-200 ng of each carvedilol enantiomer/mL plasma, and 2.5-2500 ng of each enantiomer of carvedilol, 4-hydroxyphenyl carvedilol and O-desmethyl carvedilol/mL urine. The pharmacokinetic parameters were calculated using the WinNonlin program. Enantiomer ratios within groups were evaluated by the Wilcoxon test and the Mann-Whitney test was used to determine differences in the pharmacokinetic parameters between groups. Determination of the metoprolol type oxidation phenotype showed that all patients included in the study were extensive metabolizers. Patients with type 2 DM presented no changes in the pharmacokinetics or pharmacodynamics of carvedilol when compared to the control group. Clearance (CL/F) of the R-(+)- and S-(-)-carvedilol enantiomers was significantly lower in patients with CRF on CAPD (25.17 and 27.89 L/h, respectively) compared to the control group (76.76 and 142.0 L/h). The AUCR/S ratios were 2.27 for control patients and 0.97 for patients with CRF on CAPD. Patients with CRF on CAPD showed no enantioselectivity in the pharmacokinetics of carvedilol due to the preferential plasma accumulation of the enantiomer with -blocker activity, S-(-)-carvedilol.
140

Terapia com células-tronco na nefropatia crônica experimental: é possível bloquear a progressão da doença renal? / Stem celll therapy in experimental chronic nephropathy: is it possible to block the progression of renal disease?

Cavaglieri, Rita de Cássia 08 February 2010 (has links)
Células-tronco (CT) apresentam potencial terapêutico para a doença renal pela possibilidade de regeneração tecidual e recuperação funcional, possivelmente por efeitos parácrinos. Diversos trabalhos mostraram seu efeito renoprotetor em modelo de insuficiência renal aguda. No entanto, existem poucos trabalhos que avaliaram o efeito da CT em doença renal crônica. Neste contexto, a via de inoculação e o número das CT na região da lesão podem desempenhar um papel crucial. Assim, o transplante de CT pela via EV não parece ser o mais apropriado para prover CT em número expressivo no órgão alvo. Uma técnica alternativa consiste em inocular as CT localmente, na região subcapsular renal. O objetivo do presente estudo foi analisar, em modelo experimental de doença renal crônica por nefrectomia 5/6 (Nx), a migração, a distribuição e o possível efeito renoprotetor da inoculação via subcapsular renal de 2 tipos de CT: derivadas da medula óssea (CTdmo) e mesenquimais (CTm). As CT foram coletadas de fêmur e tíbia de ratos doadores através da técnica de flushing. As CTdmo foram isoladas por gradiente de concentração e as CTm pela sua capacidade de aderência ao plástico e ambas marcadas com DAPI para a visualização no tecido. A caracterização das CT foi feita por citometria de fluxo e pela diferenciação celular in vitro. Foram realizados 2 protocolos experimentais. No protocolo I, CTdmo (1x106) foram inoculadas em ratos fêmeas e, no protocolo II, CTm (2x105) foram inoculadas em ratos machos. A região inoculada foi a subcapsula renal e os animais foram acompanhados por 15 e 30 dias. Os animais foram subdivididos nos grupos: Sham, ratos submetidos à cirurgia fictícia; Sham+CT, ratos submetidos à cirurgia fictícia que receberam CT (CTdmo ou CTm); Nx, ratos submetidos a nefrectomia 5/6; Nx+CT, Nx ratos que receberam CT (CTdmo ou CTm). Para avaliar a localização das CTdmo no tecido renal, utilizou-se a coloração de tricrômio de Masson e foi realizada uma análise semiquantitativa para avaliar o grau de infiltração. Foram analisadas a pressão arterial (PA), a albuminúria e a creatinina sérica. Para os animais que receberam CTm foi realizada a análise de parâmetros histológicos e a análise de marcadores inflamatórios, de células em atividade proliferativa, de miofibroblastos e de podócitos. Os resultados do Protocolo I avaliando a análise da infiltração no tecido renal das CTdmo marcadas com DAPI mostrou, em 5 dias, evidente infiltração das células da região subcapsular em sentido ao córtex e medula, inclusive presente em glomérulos. Ratos fêmeas Nx que receberam a inoculação das CTdmo na região da subcapsular renal não apresentaram melhora nos parâmetros que avaliaram a função renal. Protocolo II: as CTm cultivadas mostraram grande capacidade de aderência, crescimento em colônia e de diferenciação em células osteogênicas. A análise por citometria mostrou-se positiva para CD44 e CD90, com uma pequena população de células de CD34, CD45 e CD31, confirmando a presença preponderante de CTm. A inoculação de CTm em ratos Nx proporcionou um bloqueio da progressão da doença renal. Enquanto ratos Nx machos apresentaram elevada PA com 15 e 30 dias (149,6±9,1 e 191,7±2,8 mmHg) a inoculação de CTm promoveu significante redução após 30 dias (145,2±6,8 mmHg; p<0,05 vs Nx). Em ratos Nx foi observado um aumento na creatinina aos 15 e 30 dias (1,13±0,08 e 1,16±0,26 mg/dL) e a inoculação de CTm promoveu uma marcante redução aos 15 dias (0,58±0,03 mg/dL; p<0,05 vs Nx). A albuminúria foi elevada nos ratos Nx aos 15 e 30 dias (41,7±10,8 mg/24h e 138,7±33,6 mg/24h) enquanto os animais do grupo Nx+CTm aos 15 e 30 dias apresentaram diminuição significativa (4,6±1,5 mg/24h e 23,4±7,7 mg/24h; p<0,0001 vs Nx). A glomeruloesclerose do grupo Nx+CTm apresentou aos 30 dias uma redução significativa em relação ao grupo Nx (5,4±2,5% vs 22,0±6,1%, respectivamente; p<0,0001). A análise da fibrose intersticial não revelou diferença após 15 dias e 30 dias no grupo Nx+CTm em relação ao grupo Nx. Com relação ao número de macrófagos, linfócitos e de células em atividade proliferativa, os animais que receberam CTm apresentaram uma discreta diminuição de sua expressão no tecido renal. A expressão de -actina se reduziu significativamente no grupo Nx+CTm. Quanto à expressão de WT-1, específico para podócitos, os animais Nx+CTm tiveram aumento significativo da marcação em relação ao grupo Nx. Em resumo, após a inoculação de CT na região da subcapsula renal, houve marcante migração e distribuição das mesmas em direção à cortical e à medular. A inoculação de CTm proporcionou um efeito renoprotetor no modelo de nefrectomia 5/6. Sendo assim, a inoculação subcapsular renal pode representar uma importante via de inoculação, permitindo assim que um número maior de células atue na proteção da progressão da doença. / Stem cells (SCs) offer therapeutic potential for the treatment of renal diseases, due to the possibility of tissue regeneration and functional recovery. Various studies have shown renoprotection by SCs in experimental models of acute kidney disease. However, only a few studies have studied their effect in chronic kidney disease. The beneficial effect of SCs seems related to their capacity to differentiate or to secrete paracrine/endocrine factors. In this context, the inoculation route or the number of SCs homing in the injured region can play a crucial role. Therefore, transplantation of MSC through the intravenous route does not seem to be best suited for delivery of an important number of cells to the target organ. An alternative technique consists in local delivery of SCs in the subcapsular region of the kidney. The objective of the present study is to analyze the migration, distribution and potential renoprotective effect of the subcapsular inoculation of two types of SC - BSMC and mesenchymal stem cell (MSC) - in an experimental model of chronic kidney disease, the 5/6 nephrectomy (Nx). SCs were collected from the femur and tibia of donor rats by flushing. BSMC were isolated by centrifugation on a concentration gradient and MSCs were isolated by their capacity to adhere to plastic. Both types of SC were stained with DAPI to allow visualization in tissues. SC characterization was carried out by flow cytometry and differentiation in culture. Two experimental procedures were performed. In protocol I, BSMC (106 cells) were injected in female rats and in protocol II, MSCs (2x105 cells) were injected in male rats. Animals were divided into 4 groups: SHAM, sham-operated rats; SHAM+SC, sham-operated rats receiving BSMC or MSCs; Nx, rats undergoing 5/6 nephrectomy; Nx+SC, 5/6 Nx rats receiving BSMC or MSCs. We used Massons Trichrome staining and a semiquantitative analysis according to the degree of infiltration to follow the localization of BSMC in the renal tissue and to quantify their infiltration, respectively. The following parameters were studied: arterial blood pressure (AP), proteinuria (Uprot), albuminuria (Ualb) and serum creatinine (Screat). For the animals receiving SCs, analysis of histology, of inflammatory markers, of proliferating cells and of podocytes was performed. Results from Protocol I assessing DAPI-stained BSMC showed marked infiltration in 5 days from the subcapsular region to the cortex and the medulla, including presence in the glomeruli, over a period of 15 days. Female rats that received subcapsular injection of BSMC did not show improvement of the parameters used to assess kidney function. Protocol II: cultured MSCs demonstrated an ability to adhere to plastic, to grow in colonies and to differentiate in osteogenic cells. Quantitative analysis of cell markers by flow cytometry showed that isolated cells were positive for CD44 and CD90, with a small population of cells positive for CD31, CD34 and CD45, confirming a preponderant presence of MSCs. Inoculation of MSCs in Nx rats blocked the progression of the renal disease. Elevated AP in Nx rats at 15 and 30 days (149.6 ± 9.1 and 191.7 ± 2.8 mm Hg, respectively) was significantly reduced by inoculation of MSCs at 30 days (145.2 ± 6.8 mm Hg, p<0.05 vs Nx). Nx rats showed increased creatinine at 15 and 30 days (1.13 ± 0.08 and 1.16 ± 0.26 mg/dL, respectively) that was significantly reduced by injection of MSCs at 15 days (0.58 ± 0.03 mg/dL, p<0.05 vs Nx). Albuminuria was increased in Nx rats at 15 and 30 days (41.7 ± 10.8 and 138.7 ± 33.6 mg/24h, respectively) and was reduced in the Nx+MSC group at both time points (4.6 ± 1.5, and 23.4 ± 7.7 mg/24h, respectively; p<0.0001 vs Nx). Histologic analysis showed that glomerulosclerosis at 30 days in the Nx+MSC group was significantly reduced as compared to the Nx group (5.4 ± 2.5 % vs 22.0 ± 6.1 %, p<0.0001). Analysis of interstitial fibrosis did not show difference after 15 and 30 days in the Nx+MSC group compared to Nx group. Nx rats receiving MSCs showed slightly decreased inflammation markers, macrophages and lymphocytes, and proliferating cells in the renal tissue when compared to Nx rats. Analysis of myofibroblasts showed a significant decrease in expression of -smooth muscle actin in Nx+MSC rats compared to Nx rats. Podocyte number was analyzed by detection of WT-1, a specific marker. Nx rats receiving MSC had a significantly higher number of podocytes than Nx rats. In conclusion, our results show that after inoculation in the subcapsular region, SCs migrate throughout the cortex in direction of the medulla. Subcapsular inoculation of MSC provides a renoprotective effect in the model of 5/6 nephrectomy. Therefore, subcapsular inoculation could represent an important route of delivery of SCs to the kidney that allows a higher number of cells to act in the protection from progression of the disease.

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